The objectives of this project are (1) to characterize the biologically active substances from Bordetella pertussis, (2) to elucidate the mechanisms of action of these substances, and (3) to develop an effective, purified, nontoxic vaccine for whooping cough. This project emphasizes the purification and mode of action of pertussigen and other substances thought to be involved in immunizing man against whooping cough. The mechanisms of action are emphasized because pertussigen induces changes in mice that have counterparts in diseases of man. For example, pertussigen induces a marked increase in the production of IgE antibody, it increases the susceptibility to experimental allergic encephalomyelitis (EAE), it produces a marked lymphocytosis and stimulates the production of insulin. In addition, pertussigen increases susceptibility to endotoxic and anaphylactic shock and decreases resistance to various types of stress. The understanding of how pertussigen induces these changes may shed some light into how certain diseases in man (such as allergies, neurologic disorders, diabetes, excess proliferation of lymphocytes and shock) may be controlled.